Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.
Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.
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DOI：
10.1371/journal.pbio.1000086
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发表时间：
2009-04-07
期刊：
影响因子：
9.8
通讯作者：
Helfrich-Förster C
中科院分区：
文献类型：
--
作者：
Yoshii T;Ahmad M;Helfrich-Förster C
自1960年以来，磁场一直被认为是生物钟的计时器，但时钟感知和处理磁性信息的机制仍不清楚。最近，以光感受器作为磁场传感器的自由基对模型得到了相当大的支持，蓝光光感受器隐色素(CRY)被认为是一种合适的分子来介导这种磁敏性。由于CRY在生物钟神经元中表达，并且是果蝇生物钟的一个关键的光感受器，我们的目的是测试它在生物钟磁敏中的作用。对光的反应是，哭会导致时钟变慢，最终导致心律失常。我们预计，在外加磁场的存在下，哭声对时钟节律性的影响应该会改变。此外，根据自由基对假说，这种响应应该依赖于波长和施加的场强。我们测试了外加静磁场对生物钟的影响，发现暴露在这些磁场中的果蝇确实表现出更强的时钟节奏减慢。这一效应在300μT时最大，在高场强和低场强时都有所减弱。蓝光下有时钟对磁场的响应，红光下则无时钟响应，红光不能激活CREY。此外，CryB和CryOUT突变体没有表现出任何反应，在时钟神经元中过度表达CREL的果蝇对电场的反应增强。我们得出结论，果蝇的生物钟对磁场很敏感，这种敏感性取决于CRY的光激活和外加磁场强度，这与自由基对机制一致。CRY广泛存在于整个生物系统中，并被认为是候鸟磁罗盘方向的受体。目前的数据建立了果蝇的昼夜节律时钟，作为依赖哭泣的磁敏感度的模型系统。此外，鉴于哭声存在于果蝇的多个组织中，包括那些可能与苍蝇定向有关的组织，未来的研究可能会得出适用于候鸟磁罗盘的见解，甚至可能适用于人类的潜在磁场效应。磁场影响控制动物睡眠-觉醒周期的内源性时钟，但其内在机制尚不清楚。能够进行磁罗盘定位的鸟类也依赖于光，蓝光色素隐色素被提出作为导航磁传感器。在这里，我们测试了隐花色素作为果蝇黑腹果蝇时钟的光依赖磁性传感器的作用。在野生果蝇中，我们发现恒定磁场以一种剂量依赖的方式减缓了时钟的速度--但只有在蓝光存在的情况下才会如此。在缺乏功能隐花色素的突变体中，磁场对内源时钟没有显著影响，而过表达隐花色素后，这种影响增强。我们的数据表明，在蓝光激发下，隐花色素在内源性时钟中起到了磁敏传感器的作用。我们的工作支持了之前的数据，这些数据表明果蝇需要功能性的隐色素来感知磁场，这表明密码和磁场的相互作用不仅仅是鸟类的专利。果蝇的分子时钟对磁场很敏感，这种敏感方式依赖于蓝光和光致色素隐色素。
Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY) has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 μT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cryb and cryOUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system for CRY-dependent magnetic sensitivity. Furthermore, given that CRY occurs in multiple tissues of Drosophila, including those potentially implicated in fly orientation, future studies may yield insights that could be applicable to the magnetic compass of migratory birds and even to potential magnetic field effects in humans. Magnetic fields influence endogenous clocks controlling the sleep–wake cycle of animals, but the underyling mechanisms are unclear. Birds that can do magnetic compass orientation also depend on light, and the blue-light photopigment cryptochrome was proposed to act as a navigational magnetosensor. Here we tested the role of cryptochrome as a light-dependent magnetosensor of the clock in the fruit fly Drosophila melanogaster. In wild-type flies we found that constant magnetic fields slowed down the speed of the clock in a dose-dependent manner—but only in the presence of blue light. In mutants lacking functional cryptochrome, the magnetic fields had no significant effects on the endogenous clock, whereas the effects were enhanced after overexpression of cryptochrome. Our data suggest that cryptochrome works as a magnetosensor in the endogenous clock when it is excited by blue light. Our work supports previous data showing that fruit flies need functional cryptochrome to perceive a magnetic field, demonstrating that the interaction of cryptochome and magnetic fields are not just for the birds. The molecular clock of the fruit fly is sensitive to magnetic fields in a manner dependent on blue light and the photopigment cryptochrome.
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DOI：
10.1007/s003590050192
发表时间：
1998-04-01
期刊：
JOURNAL OF COMPARATIVE PHYSIOLOGY A-SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY
影响因子：
--
作者：
Helfrich-Förster, C
通讯作者：
Helfrich-Förster, C
影响因子：
4.8
作者：
Berndt, Alex;Kottke, Tilman;Wolf, Eva
通讯作者：
Wolf, Eva
DOI：
10.1101/sqb.1960.025.01.007
发表时间：
1960-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
BROWN, FA
通讯作者：
BROWN, FA
影响因子：
3.5
作者：
Helfrich-Förster, C
通讯作者：
Helfrich-Förster, C
影响因子：
64.5
作者：
Emery, P;So, WV;Rosbash, M
通讯作者：
Rosbash, M